Human cancer-prone genetic diseases are being studied in order to identify groups of people with an increased susceptibility to environmental carcinogenesis. We are attempting to determine the clinical consequences as well as the molecular basis of their cellular hypersensitivity. Patients with xeroderma pigmentosum (XP) and ataxia telangiectasia (AT), diseases with ultraviolet and X-ray sensitivity, respectively, and patients with familial malignant melanoma (dysplastic nevus syndrome) are being studied. Detailed examinations of the clinical features of affected individuals are being made. A registry of XP patients is being established. Cultures of skin and blood are being established and the effects on cell survival, mutagenesis, DNA synthesis and repair, histone synthesis and chromosome integrity after treatment with DNA damaging agents are being examined. We are using recombinant DNA technology to attempt to clone the genes responsible for UV sensitivity in XP cells. These studies may give insights into mechanisms of cancer induction and suggest modes of cancer prophylaxis. In addition, these diseases serve as models for studies of human environmental carcinogenesis.